Chromosome 21 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 21 is the smallest human chromosome, spanning almost 47 million base pairs (the building material of DNA) and representing about 1.5 percent of the total DNA in cells.

In 2000, researchers working on the Human Genome Project announced that they had determined the sequence of base pairs that make up this chromosome. Chromosome 21 was the second human chromosome to be fully sequenced.

Identifying genes on each chromosome is an active area of genetic research. Because researchers use different approaches to predict the number of genes on each chromosome, the estimated number of genes varies. Chromosome 21 likely contains between 200 and 400 genes.

Chromosomal conditions

The following conditions are caused by changes in the structure or number of copies of chromosome 21:

Cancers: Rearrangements (translocations) of genetic material between chromosome 21 and other chromosomes have been associated with several types of cancer. For example, acute lymphoblastic leukemia (a type of blood cancer most often diagnosed in childhood) has been associated with a translocation between chromosomes 12 and 21. Another form of leukemia, acute myeloid leukemia, has been associated with a translocation between chromosomes 8 and 21.

Down syndrome: Down syndrome is most often caused by trisomy 21. Trisomy 21 means that each cell in the body has three copies of chromosome 21 instead of the usual two copies. Down syndrome can also result from an extra copy of chromosome 21 in only some of the body's cells (mosaic Down syndrome).

In a small percentage of cases, Down syndrome is caused by a rearrangement of chromosomal material between chromosome 21 and another chromosome. As a result, a person has the usual two copies of chromosome 21, plus extra material from chromosome 21 attached to another chromosome. These cases are called translocation Down syndrome.
Researchers believe that extra copies of genes on chromosome 21 disrupt the course of normal development, causing the characteristic features of Down syndrome and the increased risk of medical problems associated with this disorder.
other chromosomal conditions

Other changes in the number or structure of chromosome 21 can have a variety of effects, including mental retardation, delayed development, and characteristic facial features. In some cases, the signs and symptoms are similar to those of Down syndrome. Changes to chromosome 21 include a missing segment of the chromosome in each cell (partial monosomy 21) and a circular structure called ring chromosome 21. A ring chromosome occurs when both ends of a broken chromosome are reunited.

Duplication in Amyloid precursor protein (APP) locus (duplicated segment varies in length but includes APP) on Chromosome 21 was found to cause early onset familial Alzheimer's disease (AD) in a french family set (Rovelet-Lecrux et al) and a dutch family set (Sleegers et al). Compared to AD caused by missense mutations in APP, the frequency of the AD caused by APP duplications is significant. ALL the patients that have an extra copy of APP gene due to the locus duplication show AD with severe Cerebral amyloid angiopathy (CAA).